Iron is a specific cofactor for distinct oxidation- and aggregation-dependent Aβ toxicity mechanisms in a Drosophila model.

ABSTRACT: Metals, including iron, are present at high concentrations in amyloid plaques in individuals with Alzheimer's disease, where they are also thought to be cofactors in generating oxidative stress and modulating amyloid formation. In this study, we present data from several Drosophila models of neurodegenerative proteinopathies indicating that the interaction between iron and amyloid beta peptide (Aβ) is specific and is not seen for other aggregation-prone polypeptides. The interaction with iron is likely to be important in the dimerisation of Aβ and is mediated by three N-terminal histidines. Transgenic fly lines systematically expressing all combinations of His>Ala substitutions in Aβ were generated and used to study the pathological role of these residues. Developmental eye phenotypes, lon

SUBMITTER: Ott S 

PROVIDER: S-EPMC4486857 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature